Genetic and biochemical determinants of serum concentrations of monocyte chemoattractant protein-1, a potential neural tube defect risk factor.
BACKGROUND
Women with the AA genotype at the (-2518)A>G promoter polymorphism of CCL-2, which encodes the potent pro-inflammatory chemokine monocyte chemoattractant protein 1 (MCP-1), may be at increased risk for having offspring affected by spina bifida. As the A allele at this locus has been associated with decreased transcription of MCP-1 mRNA relative to the G allele, the observed genetic association suggests that the risk of spina bifida may be increased in the offspring of women with low MCP-1 levels. The present study was undertaken to identify potential determinants of MCP-1 levels in women of reproductive age.


METHODS
A small cohort of Caucasian and African-American women of reproductive age was recruited to participate in an exploratory investigation of the determinants of several disease-related, biochemical phenotypes, including MCP-1. Subjects completed a brief questionnaire and provided a fasting blood sample for biochemical and genetic studies. Potential biochemical, genetic, and lifestyle factors were assessed for their association with MCP-1 levels using linear regression analyses.


RESULTS
In this cohort, MCP-1 levels were significantly higher in Caucasians as compared to African-Americans. Further, among women of both races, there was evidence that MCP-1 levels were associated with smoking status, MTHFR 677C>T genotype, and red blood cell tetrahydrofolate levels.


CONCLUSIONS
The results of these analyses indicate that, if maternal CCL-2 genotype is related to the risk of spina bifida, this relationship is likely to be more complex than initially hypothesized, perhaps depending upon folate intake, MTHFR 677C>T genotype, the distribution of folate derivatives, and immune/inflammatory activity.
Lu
Zhi-Yong
ZY
Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA.
Morales
Megan
M
Khartulyari
Stephanie
S
Mei
Minghua
M
Murphy
Kristen M
KM
Stanislawska-Sachadyn
Anna
A
Summers
Carolyn M
CM
Huang
Yuehua
Y
Von Feldt
Joan M
JM
Blair
Ian A
IA
Mitchell
Laura E
LE
Whitehead
Alexander S
AS
D000328:Adult; D001741:Black or African American; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D009436:Neural Tube Defects / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D044465:White People
D018932:Chemokine CCL2; D042965:Methylenetetrahydrofolate Reductase (NADPH2)